Usefulness of Tissue Doppler Velocity and Strain Dyssynchrony for Predicting Left Ventricular Reverse Remodeling Response After

Cardiac Resynchronization Therapy

Cheuk-Man Yu, MDa,*, John Gorcsan III, MDb, Gabe B. Bleeker, MDc, Qing Zhang, MDa, Martin J. Schalij, MD, PhDc, Matthew S. Suffoletto, MDb, Jeffrey Wing-Hong Fung, MDa, David Schwartzman, MDb, Yat-Sun Chan, MRCPa, Masaki Tanabe, MDb, and Jeroen J. Bax, MD, PhDc
The assessment of systolic dyssynchrony by echocardiography is useful in predicting a favorable response to cardiac resynchronization therapy (CRT). Tissue Doppler velocity and tissue Doppler longitudinal strain have been suggested for this purpose. This study compared parameters of systolic dyssynchrony derived from these 2 imaging modalities for their predictive values of CRT response. Two hundred fty-six patients from 3 different centers who received CRT were followed for 6 3 months. Parameters of systolic dyssynchrony based on tissue Doppler velocity and strain imaging were assessed for the prediction of left ventricular (LV) reverse remodeling (reduction of LV end-systolic volume >15%). These included time to peak systolic velocity (or peak strain) of 12 LV segments to calculate the SD (Ts-SD or T-SD), maximal difference in delay (Ts-Diff or T-Diff), and opposite wall delay (Ts-OW or T-OW). The septal-to-lateral delay (Ts-Sep-Lat or TSep-Lat) was also measured. LV reverse remodeling, dened as improvement in endsystolic volume >15%, was observed in 141 patients (55%). All 4 tissue velocity parameters predicted LV reverse remodeling, and the areas under the receiver-operating characteristic curves were 0.86, 0.85, 0.84, and 0.79 for Ts-SD, Ts-Diff, Ts-OW, and Ts-Sep-Lat, respectively (all p <0.001). The cut-off values derived from receiver-operating characteristic curve analysis were 33 ms for Ts-SD, 100 ms for Ts-Diff, 90 ms for Ts-OW, and 60 ms for Ts-Sep-Lat, and their sensitivities were 93%, 92%, 81%, and 70%, with specicities of 78%, 68%, 80%, and 76%, respectively. In contrast, none of the longitudinal strain parameters predicted LV reverse remodeling. The areas under the receiver-operating characteristic curves ranged from 0.49 to 0.53 (all p NS). The same conclusions were obtained in subgroup analyses of QRS duration (120 to 150 vs >150 ms) and ischemic or nonischemic cause of heart failure. In conclusion, parameters of tissue Doppler longitudinal velocity, but not longitudinal strain, predicted LV reverse remodeling after CRT. 2007 Elsevier Inc. All rights reserved. (Am J Cardiol 2007;100:12631270)

Despite the compelling evidence of the benets of cardiac resynchronization therapy (CRT), the lack of a clinical or reverse remodeling response has been observed in about 1/3 of patients.1,2 In the past few years, the role of echocardiography to assess mechanical dyssynchrony in patients receiving CRT, in particular tissue Doppler imaging (TDI), has undergone continuous exploration.311 TDI is used to examine the time to peak systolic velocity from 2 left ventricular (LV) segments to calculate parameters of systolic dyssynchrony. Recently, other TDI postprocessing approaches that calculate longitudinal strain have been explored,

although the results of studies have not been uniform, with 1 study reporting a fair correlation with LV reverse remodeling after CRT and another study reporting a lack of a relation.12,13 Because the discussion of which echocardiographic technique to use continues, in this study, we aimed to compare parameters of systolic dyssynchrony derived from longitudinal tissue Doppler velocity and tissue Doppler strain imaging for the prediction of LV reverse remodeling after CRT in a large patient population, with data derived from 3 different clinical centers. This large patient sample also permitted the evaluation of the inuence of QRS width (150 vs 120 to 150 ms) and the cause of heart failure (ischemic vs nonischemic). Methods Two hundred fty-six patients with heart failure (mean age 65.3 11.2 years; 74% men) who received CRT at 3 different centers were included in the study. The mean follow-up duration was 6 3 months. The inclusion criteria for CRT were compatible with current guidelines, including New York
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a Division of Cardiology, Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong; bCardiovascular Institute, University of Pittsburgh, Pittsburgh, Pennsylvania; and cDepartment of Cardiology, Leiden University Medical Center, Leiden, The Netherlands. Manuscript received March 27, 2007; revised manuscript received and accepted May 22, 2007. *Corresponding author: Tel: 852-2632-3594; fax: 852-2637-5643. E-mail address: cmyu@cuhk.edu.hk (C.-M. Yu).

0002-9149/07/$ see front matter 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.amjcard.2007.05.060

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Figure 1. Ts-OW. In each of the apical (4-, 2-, and 3-chamber) views, the maximal differences in Ts between the opposite wall segments at the basal and mid levels were identied (sampling points indicted by arrows). Then the largest value among the 3 views was taken as Ts-OW. In this patient, the opposite wall delays in the 4-, 2-, and 3-chamber views were 110, 90, and 120 ms, respectively. Therefore, the Ts-OW was 120 ms. Ts-SD was 51 ms and Ts-Diff was 130 ms.

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Figure 2. T. In each of the apical (4-, 2-, and 3-chamber) views, the T values in 4 basal and mid segments were measured with reference to the QRS complex (sampling points indicted by arrows). Using algorithms similar to tissue Doppler velocity measurement, T-SD was 79 ms, T-Diff was 210 ms, T-OW was 210 ms, and T-Sep-Lat was 170 ms.

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Table 1 Changes in left ventricular end-diastolic volumes, end-systolic volumes, and ejection fractions in patients who received cardiac resynchronization therapy in the whole study population and in subgroups according to QRS duration and cause of heart failure Whole Group (n 256) LVEDV (cm3) Baseline CRT p value LVESV (cm3) Baseline CRT p value LVEF (%) Baseline CRT p value 223 86 196 81 0.001 173 79 141 73 0.001 23.7 7.9 30.9 10.0 0.001 QRS 120150 ms (n 77) 196 74 178 69 0.001 148 63 125 58 0.001 25.5 6.7 31.7 9.1 0.001 QRS 150 ms (n 179) 234 88* 203 84 0.001 184 83* 148 78 0.001 22.9 8.2 30.5 10.4 0.001 Ischemic (n 144) 223 82 202 75 0.001 173 75 145 66 0.001 23.7 7.1 30.1 9.4 0.001 Nonischemic (n 112) 223 91 188 87 0.001 174 85 136 81 0.001 23.7 8.8 32.0 10.6 0.001

* p 0.001; p 0.01; p 0.05 versus wide QRS (120 to 150 ms). LVEDV LV end-diastolic volume; LVEF LV ejection fraction; LVESV LV end-systolic volume.

Heart Association class III (88%) or IV (12%) heart failure despite optimal pharmacologic therapy, evidence of LV systolic dysfunction (LV ejection fraction 35%), and QRS duration 120 ms. The causes of heart failure were ischemic in 144 patients (56%) and nonischemic in 112 patients (44%). The study protocol was approved by the ethics committees, and informed consent was obtained. Biventricular devices were implanted as previously described.1,14 The LV pacing lead was inserted by a transvenous approach through the coronary sinus and targeted into either the lateral or posterolateral cardiac vein. Conventional right ventricular and right atrial leads were implanted. The choices of CRT device included InSync, InSync III, InSync Marquis, and InSync Sentry (Medtronic Inc., Minneapolis, Minnesota), as well as Contak TR, Contak TR II, and Contak CD (Guidant Inc., St. Paul, Minnesota). Standard 2-dimensional and Doppler echocardiography was performed as previously described,14,15 and all devices were programmed in simultaneous biventricular pacing mode. TDI was performed as previously reported (Vivid 7; GE-Vingmed Ultrasound AS, Horten, Norway).8,14 All 3 centers had similar echocardiographic facilities for image acquisition and off-line analysis. During on-line image acquisition, 3 cardiac cycles were analyzed in a blinded fashion, and average values of the different parameters were derived. The LV volumes and ejection fractions were assessed using the biplane Simpsons equation in the apical 4and 2-chamber views. Two-dimensional color-coded TDI was performed in the 3 apical views (apical 4- and 2-chamber and long-axis views) at 2 institutions (n 174; Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, and the Cardiovascular Institute, University of Pittsburgh, Pittsburgh, Pennsylvania) and in the apical 4-chamber view at all institutions to assess longitudinal dynamics, as previously described.6 Images were optimized for pulse repetition frequency, color saturation, sector size, and depth and allowed a highest possible frame rate of 100 frames/s. Images were analyzed off-line in a blinded fashion (EchoPac-PC version 3.1.3; GE-Vingmed Ultrasound AS) using the 6-basal and 6-mid segmental model of the left ventricle, as previously described.4,14 During ofine

Table 2 Comparison of clinical and echocardiographic characteristics before and after cardiac resynchronization therapy in responders and nonresponders of left ventricular reverse remodeling Parameter Ts-SD Ts-Diff Ts-OW Ts-Sep-Lat T-SD T-Diff T-OW T-Sep-Lat Nonresponders 28.6 10.8 91 29 79 25 42 44 65 31 170 86 130 59 109 88 Responders 46.4 12.5 137 34 115 29 90 52 67 28 175 74 123 75 109 98 p Value 0.001 0.001 0.001 0.001 NS NS NS NS

analysis, a sampling window of 6 12 mm was used for tissue Doppler velocity and 12 mm for strain measurements. The ejection interval was determined from aortic valve opening and aortic valve closure from LV outow tract Doppler, and postsystolic peaks were not included in the analysis. Tissue synchronization imaging was activated to color-coded time to peak velocity in the ejection phase and assisted in placing regions of interest, but dyssynchrony analysis was performed at the myocardial velocity curves in all cases.9,16 Regions of interest were placed in the basal and midventricular walls and manually adjusted up and down and left to right within the segment to create the myocardial velocity curve and determine the region with the most reproducible peaks. The time to peak myocardial systolic velocity during the ejection phase (Ts) was measured with reference to the onset of the QRS complex.4,8 Parameters of systolic dyssynchrony were calculated, including (1) the SD of Ts from 12 LV segments (Ts-SD); (2) the maximal difference in Ts from 12 LV segments (Ts-Diff); (3) opposite wall delay in Ts from 12 LV segments (Ts-OW) (in this method, the largest difference in Ts between opposing walls was measured in each of the 3 apical views [2 basal and 2 mid segments per view], and the maximal value of delay among these 3 views was selected [Figure 1]); and (4) septal-to-lateral delay in Ts (Ts-Sep-Lat). Tissue Doppler strain imaging was performed by program-

Heart Failure/Velocity Versus Strain Prediction for CRT 0.001 0.001 0.001 0.001 NS NS NS NS NS

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Table 3 Areas under the receiver-operating characteristic curves of various parameters of systolic dyssynchrony for predicting left ventricular reverse remodeling after cardiac resynchronization therapy

Nonischemic

p Value AUC Ischemic p Value AUC QRS 150 ms p Value AUC 95% CI 95% CI 95% CI

0.81 0.78 0.77 0.75 0.40 0.41 0.45 0.42

0.700.92 0.660.89 0.650.89 0.680.83 0.270.53 0.280.54 0.310.59 0.290.55

0.001 0.001 0.001 0.001 NS NS NS NS

0.85 0.85 0.83 0.76 0.53 0.54 0.59 0.52 0.62

0.760.94 0.770.94 0.730.92 0.670.84 0.400.66 0.410.67 0.460.72 0.390.65 0.520.71

0.001 0.001 0.001 0.001 NS NS NS NS 0.02

0.87 0.85 0.85 0.84 0.57 0.56 0.54 0.48 0.57

0.770.97 0.740.96 0.740.96 0.760.92 0.410.72 0.410.71 0.380.70 0.330.64 0.460.68

QRS 120150 ms

Figure 3. ROC curves for the identication of LV reverse remodeling in patients who received CRT for the parameters based on Ts or T in the whole study population. (A) Velocity parameters included Ts-SD, Ts-Diff, Ts-OW, and Ts-Sep-Lat. (B) Strain parameters included T-SD, T-Diff, T-OW, and T-Sep-Lat.

0.850.99 0.850.99 0.821.00 0.750.93 0.500.79 0.500.79 0.520.81 0.410.71

95% CI

0.001 0.001 0.001 0.001 NS (0.06) NS (0.06) 0.04 NS

p Value

ming the sampling points of 6 12 mm at different myocardial segments. Tissue strain () was calculated using the formula (L L0)/L0 100%, where L is the instantaneous length and L0 is the original length. The time to peak negative strain (T) was measured. Using methods similar to that of longitudinal tissue Doppler velocity, parameters of systolic dyssynchrony were measured (Figure 2), including (1) the SD of T in the LV segments (T-SD); (2) the maximal difference in T in the LV segments (T-Diff); (3) opposite wall delay in T in the LV segments (T-OW); and (4) septal-to-lateral delay in T (T-Sep-Lat). For measuring the timing of tissue velocity, the interobserver variability ranged from 5% to 10%, and the intraobserver variability was 4% to 5%. For measuring the timing of tissue strain, these percentages were 8% to 13% and 7% to 10%, respectively. For statistical comparison of parametric variables before and after CRT, the paired-sample Students t test was used. Receiver-operating characteristic (ROC) curves were analyzed for the area under the curves to determine the optimal cut-off values of systolic dyssynchrony that predicted LV reverse remodeling after CRT. All parametric data are ex-

Ts-SD Ts-Diff Ts-OW Ts-Sep-Lat T-SD T-Diff T-OW T-SD-Sep-Lat QRS duration

Parameter

AUC area under the ROC curve; CI condence interval.

AUC All Patients p Value AUC 95% CI

0.86 0.85 0.84 0.79 0.53 0.54 0.56 0.49 0.60

0.800.93 0.780.92 0.770.91 0.730.84 0.430.63 0.440.63 0.460.66 0.390.59 0.530.67

0.001 0.001 0.001 0.001 NS NS NS NS 0.007

0.92 0.92 0.91 0.84 0.65 0.65 0.66 0.56

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Table 4 Cut-off values, sensitivities, and specicities of various parameters of systolic dyssynchrony for predicting left ventricular reverse remodeling after cardiac resynchronization therapy Parameter Cutoff (ms) All Patients QRS 120150 ms QRS 150 ms Ischemic Nonischemic

Sensitivity Specicity Sensitivity Specicity Sensitivity Specicity Sensitivity Specicity Sensitivity Specicity (%) (%) (%) (%) (%) (%) (%) (%) (%) (%) Ts-SD Ts-SD-Diff Ts-OW Ts-Sep-Lat QRS duration 33 100 90 60 145 93 92 81 70 81 73 68 80 76 36 96 96 88 63 79 76 91 86 94 90 78 73 67 59 67 71 92 92 74 66 77 74 71 84 74 37 97 94 89 75 85 77 68 73 78 36

pressed as mean SD. A p value 0.05 was considered statistically signicant. Results There were reductions in LV end-diastolic (p 0.001) and end-systolic (p 0.001) volumes, with improvements in LV ejection fractions (p 0.001), after CRT (Table 1). A response of LV reverse remodeling was dened as a reduction in LV end-systolic volume of 15%,7,8,14 which was observed in 141 patients (55%). The other 115 patients (45%), who had reductions in LV end-systolic volume 15%, were classied as nonresponders. The baseline LV sizes and ejection fractions were similar between responders and nonresponders of LV reverse remodeling (Table 1). However, responders exhibited more severe systolic dyssynchrony when parameters of tissue Doppler velocity were compared. Tissue Doppler strain parameters showed minimal difference in systolic dyssynchrony between responders and nonresponders (Table 2). Table 3 lists the areas under the ROC curves of the tissue Doppler velocity parameters that predicted LV reverse remodeling. The areas under the ROC curves were similar for Ts-SD, Ts-Diff, and Ts-OW (0.84 to 0.86, all p 0.001) and slightly less for Ts-Sep-Lat (0.79, p 0.001; Figure 3). Table 4 lists the optimal cut-off values for the prediction of LV reverse remodeling response by different tissue Doppler velocity echocardiographic parameters, with their optimal sensitivities and specicities derived from the shoulders of the ROC curves. All parameters derived from 12 LV segments had reasonably high sensitivities to predict LV reverse remodeling. A cut-off value for Ts-SD of 33 ms yielded a sensitivity of 93% and a specicity of 73%. A cut-off value for Ts-Diff of 100 ms had sensitivity and specicity of 92% and 68%, respectively. A cut-off value for Ts-OW of 90 ms resulted in sensitivity and specicity of 81% and 80%, respectively, and a cut-off value for Ts-SepLat of 60 ms resulted in sensitivity and specicity of 70% and 76%, respectively. In contrast to tissue Doppler velocity, none of the parameters of systolic dyssynchrony derived from tissue Doppler strain were able to predict LV reverse remodeling. All the areas under the ROC curves were close to the reference value of 0.50 (Table 3, Figure 3). The predictive value of QRS duration on electrocardiography was also evaluated. The area under the ROC curve was 0.60 (p 0.007). A cut-off value of 145 ms had a

Figure 4. ROC curves for the identication of LV reverse remodeling in patients who received CRT for the subgroups with QRS durations of 120 to 150 ms (A) and QRS durations 150 ms (B). These parameters were based on tissue velocity measurement, including Ts-SD, Ts-Diff, Ts-OW, and Ts-Sep-Lat.

sensitivity of 81% and a specicity of 36% to predict LV reverse remodeling. Seventy-seven patients (30%) had QRS durations of 120 to 150 ms, and 179 patients (70%) had QRS durations 150 ms. The improvements of LV end-diastolic volumes, endsystolic volumes, and ejection fractions were consistently observed in the 2 subgroups, although patients with QRS durations 150 ms appeared to have higher baseline LV volumes and lower ejection fractions compared with patients with QRS durations of 120 to 150 ms (Table 1).

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(n 67 [60%]), although the difference was not statistically signicant (chi-square 1.44, p NS). The areas under the ROC curves of various tissue Doppler velocity and strain parameters are listed in Table 3. The areas under the curves were similar for ischemic and nonischemic subjects for parameters based on 12 LV segments. On the basis of the aforementioned cut-off values, all TDI parameters had good sensitivities (ranging from 74% to 97%) to predict reverse remodeling after CRT, with somewhat lower specicities (ranging from 68% to 84%) (Table 4 and Figure 5). Discussion This study is the largest to date that examined the predictive values of TDI-derived echocardiographic parameters of intraventricular dyssynchrony on LV reverse remodeling after CRT, with data collected from 3 independent centers. Also, the present study compared a large number of myocardial longitudinal velocity and strain parameters of dyssynchrony in the same study population. With this approach, the superiority of longitudinal tissue Doppler velocity over tissue Doppler strain parameters of LV dyssynchrony to predict response to CRT was clearly demonstrated. Furthermore, similar results were obtained in 2 subanalyses focusing on QRS duration and the cause of heart failure. Although CRT is an established therapy for advanced heart failure with electromechanical delay, the consistent occurrence of nonresponse has prompted the development of noninvasive imaging tools to predict a favorable response after CRT.311 An important issue is the precise denition of response. In the present study, response to CRT was dened by a reduction in LV end-systolic volume of 15%. Although response can also be dened according to improvement in clinical parameters, including symptoms or exercise capacity, these end points are subject to the placebo effect, as shown in large multicenter trials.1,17 Moreover, recent data have shown that LV reverse remodeling is associated with superior long-term survival, whereas improvement in symptoms was not associated with better outcomes, suggesting that LV reverse remodeling may be the preferred end point.18 The use of echocardiographic parameters to assess prepacing systolic mechanical dyssynchrony has been reported to be useful to predict a favorable response to CRT, in particular to predict LV reverse remodeling and improvement in systolic function.311 Among various echocardiographic techniques, tissue Doppler velocity has been validated extensively.4 10 Recently, more complex technology, such as tissue Doppler strain imaging, has been evaluated to predict response to CRT.12,13 Recent data obtained from 37 patients with heart failure suggested that dyssynchrony assessed from strain imaging (T-SD) correlated with either LV reverse remodeling or improvement in the ejection fraction after CRT.13 At the same time, however, another study in 55 patients did not conrm the usefulness of T-SD or T-Diff.12 The present study is the largest to conrm the lack of predictive values of tissue Doppler strain parameters to predict LV reverse remodeling or improvement in systolic function after CRT. The areas under the ROC curves were small for all the strain parameters studied. Although TDI longitudinal strain may be helpful as an adjunct in

Figure 5. ROC curves for the identication of LV reverse remodeling in patients who received CRT for the subgroups with ischemic (A) and nonischemic (B) causes of heart failure. These parameters were based on tissue velocity measurement, including Ts-SD, Ts-Diff, Ts-OW and Ts-Sep-Lat.

The prevalence of responders was lower among the patients with QRS durations of 120 to 150 ms (n 35 [46%]) than the patients with QRS durations 150 ms (n 106 [59%]) (chi-square 4.12, p 0.04). Ts-SD, Ts-Diff, and Ts-OW had the highest areas under the ROC curves (0.91 to 0.92, all p 0.001) to predict LV reverse remodeling in the group with QRS durations of 120 to 150 ms (Table 3). Interestingly, the areas under the ROC curves for all tissue Doppler velocity parameters were consistently larger for the group with QRS durations of 120 to 150 ms compared with patients with QRS durations 150 ms (Figure 4). Consequently, for the same cut-off values, the sensitivities to predict response to CRT were comparable between the 2 groups, whereas the specicities were higher in patients with QRS durations of 120 to 150 ms (Table 4). One hundred forty-four patients (56%) had ischemic causes of heart failure, and the other 112 patients (44%) had causes that were nonischemic in origin. The 2 subgroups showed signicant improvements in LV volumes and ejection fractions, and there was no difference in the baseline and follow-up values between the 2 subgroups. The prevalence of responders of LV reverse remodeling was slightly less in the ischemic patients (n 74 [51%]) compared with nonischemic patients

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The American Journal of Cardiology (www.AJConline.org) tissue Doppler echocardiography to evaluate left ventricular dyssynchrony before and after biventricular pacing in patients with idiopathic dilated cardiomyopathy. Am J Cardiol 2003;91:94 97. Dohi K, Suffoletto MS, Schwartzman D, Ganz L, Pinsky MR, Gorcsan J III. Utility of echocardiographic radial strain imaging to quantify left ventricular dyssynchrony and predict acute response to cardiac resynchronization therapy. Am J Cardiol 2005;96:112116. Notabartolo D, Merlino JD, Smith AL, DeLurgio DB, Vera FV, Easley KA, Martin RP, Leon AR. Usefulness of the peak velocity difference by tissue Doppler imaging technique as an effective predictor of response to cardiac resynchronization therapy. Am J Cardiol 2004;94: 817 820. Yu CM, Fung JW, Zhang Q, Chan CK, Chan YS, Lin H, Kum LC, Kong SL, Zhang Y, Sanderson JE. Tissue Doppler imaging is superior to strain rate imaging and postsystolic shortening on the prediction of reverse remodeling in both ischemic and nonischemic heart failure after cardiac resynchronization therapy. Circulation 2004;110:66 73. Gorcsan J III, Kanzaki H, Bazaz R, Dohi K, Schwartzman D. Usefulness of echocardiographic tissue synchronization imaging to predict acute response to cardiac resynchronization therapy. Am J Cardiol 2004;93:1178 1181. Bax JJ, Bleeker GB, Marwick TH, Molhoek SG, Boersma E, Steendijk P, van der Wall EE, Schalij MJ. Left ventricular dyssynchrony predicts response and prognosis after cardiac resynchronization therapy. J Am Coll Cardiol 2004;44:1834 1840. Suffoletto MS, Dohi K, Cannesson M, Saba S, Gorcsan J III. Novel speckle-tracking radial strain from routine black-and-white echocardiographic images to quantify dyssynchrony and predict response to cardiac resynchronization therapy. Circulation 2006;113:960 968. Yu CM, Zhang Q, Chan YS, Chan CK, Yip GW, Kum LC, Wu EB, Lee PW, Lam YY, Chan S, Fung JW. Tissue Doppler velocity is superior to displacement and strain mapping in predicting left ventricular reverse remodeling response after cardiac resynchronization therapy. Heart 2006;19:422 428. Mele D, Pasanisi G, Capasso F, De Simone A, Morales MA, Poggio D, Capucci A, Tabacchi G, Sallusti L, Ferrari R. Left intraventricular myocardial deformation dyssynchrony identies responders to cardiac resynchronization therapy in patients with heart failure. Eur Heart J 2006;27:1070 1078. Yu CM, Chau E, Sanderson JE, Fan K, Tang MO, Fung WH, Lin H, Kong SL, Lam YM, Hill MR, Lau CP. Tissue Doppler echocardiographic evidence of reverse remodeling and improved synchronicity by simultaneously delaying regional contraction after biventricular pacing therapy in heart failure. Circulation 2002;105:438 445. Bargiggia GS, Bertucci C, Recusani F, Raisaro A, de Servi S, ValdesCruz LM, Sahn DJ, Tronconi L. A new method for estimating left ventricular dP/dt by continuous wave Doppler-echocardiography. Validation studies at cardiac catheterization. Circulation 1989;80:1287 1292. Yu CM, Zhang Q, Fung JW, Chan HC, Chan YS, Yip GW, Kong SL, Lin H, Zhang Y, Sanderson JE. A novel tool to assess systolic asynchrony and identify responders of cardiac resynchronization therapy by tissue synchronization imaging. J Am Coll Cardiol 2005;45:677 684. Young JB, Abraham WT, Smith AL, Leon AR, Lieberman R, Wilkoff B, Canby RC, Schroeder JS, Liem LB, Hall S, Wheelan K. Combined cardiac resynchronization and implantable cardioversion debrillation in advanced chronic heart failure: the MIRACLE ICD trial. JAMA 2003;289:26852694. Yu CM, Bleeker GB, Fung JW, Schalij MJ, Zhang Q, van der Wall EE, Chan YS, Kong SL, Bax JJ. Left ventricular reverse remodeling but not clinical improvement predicts long-term survival after cardiac resynchronization therapy. Circulation 2005;112:1580 1586. Bax JJ, Marwick TH, Molhoek SG, Bleeker GB, van Erven L, Boersma E, Steendijk P, van der Wall EE, Schalij MJ. Left ventricular dyssynchrony predicts benet of cardiac resynchronization therapy in patients with end-stage heart failure before pacemaker implantation. Am J Cardiol 2003;92:1238 1240. Yu CM, Fung JW, Chan CK, Chan YS, Zhang Q, Lin H, Yip GW, Kum LC, Kong SL, Zhang Y, Sanderson JE. Comparison of efcacy of reverse remodeling and clinical improvement for relatively narrow and wide QRS complexes after cardiac resynchronization therapy for heart failure. J Cardiovasc Electrophysiol 2004;15:1058 1065.

patients with high data quality, it was not consistently predictive in this large series of patients studied. An important problem with such strain calculation is that the scan line angle of incidence may not be aligned precisely with the direction of shortening of the LV wall. This occurs in dilated, spherically distorted left ventricles, which are often encountered in the CRT population. A more recent approach to assess regional strain and dyssynchrony using speckle tracking from routine grayscale echocardiographic images that is not affected by Doppler angle of incidence has been more promising to predict response to CRT.11 In the present study, myocardial velocity parameters derived from TDI predicted a favorable volumetric response to CRT. The areas under the ROC curves that predicted reverse remodeling response were consistently high for all the parameters of systolic dyssynchrony derived from 12 LV segments. Among these parameters, the cut-off values derived from the ROC curves for Ts-SD and Ts-Diff had high sensitivities, whereas those derived from Ts-OW had relatively higher specicities. Ts-Sep-Lat, which examined only septal-to-lateral wall delay in a single apical view, also had reasonably high sensitivity and specicity. Furthermore, the cut-off values derived from the ROC curves substantiated previous ndings.10,19 Another important observation is that the predictive values of TDI velocity parameters are consistently present in different subgroups, namely, those with different degrees of widening of the QRS complex (120 to 150 or 150 ms) and causes of heart failure (ischemic or nonischemic). Because the study included a large population, it allowed for meaningful analyses and subgroup comparisons. It was interesting to note that in patients with QRS durations 150 ms, the specicity of the dyssynchrony parameters tended to be lower than in patients with QRS durations of 120 to 150 ms. This may have been related to the fact that a wide QRS duration of 150 ms already preselected those patients with more severe systolic dyssynchrony, resulting in a higher response rate compared with patients with less wide QRS complexes.20 The present study did not reveal an obvious difference in predictive value for LV reverse remodeling between ischemic and nonischemic subgroups, although the response rate to CRT has been shown previously to be lower in ischemic than nonischemic subgroups.1 In fact, the cut-off values derived from the whole study population that predicted LV reverse remodeling after CRT could also be applied to these subgroups, yielding similar predictive values.
1. Abraham WT, Fisher WG, Smith AL, DeLurgio DB, Leon AR, Loh E, Kocovic DZ, Packer M, Clavell AL, Hayes DL, et al. Cardiac resynchronization in chronic heart failure. N Engl J Med 2002;346:1845 1853. 2. Bax JJ, Abraham T, Barold SS, Breithardt OA, Fung JW, Garrigue S, Gorcsan J III, Hayes DL, Kass DA, Knuuti J, et al. Cardiac resynchronization therapy: Part 1issues before device implantation. J Am Coll Cardiol 2005;46:21532167. 3. Pitzalis MV, Iacoviello M, Romito R, Massari F, Rizzon B, Luzzi G, Guida P, Andriani A, Mastropasqua F, Rizzon P. Cardiac resynchronization therapy tailored by echocardiographic evaluation of ventricular asynchrony. J Am Coll Cardiol 2002;40:16151622. 4. Yu CM, Fung JWH, Lin H, Zhang Q, Sanderson JE, Lau CP. Predictors of left ventricular reverse remodeling after cardiac resynchronization therapy for heart failure secondary to idiopathic dilated or ischemic cardiomyopathy. Am J Cardiol 2003;91:684 688. 5. Bax JJ, Molhoek SG, van Erven L, Voogd PJ, Somer S, Boersma E, Steendijk P, Schalij MJ, van der Wall EE. Usefulness of myocardial

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